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Osteocyte Apoptosis Controls Activation of Intracortical Resorption in Response to Bone Fatigue

By Luis Cardoso, Brad C Herman, Olivier Verborgt, Damien Laudier, Robert J Majeska and Mitchell B Schaffler


Osteocyte apoptosis is spatially and temporally linked to bone fatigue–induced microdamage and to subsequent intracortical remodeling. Specifically, osteocytes surrounding fatigue microcracks in bone undergo apoptosis, and those regions containing apoptotic osteocytes co-localize exactly with areas subsequently resorbed by osteoclasts. Here we tested the hypothesis that osteocyte apoptosis is a key controlling step in the activation and/or targeting of osteoclastic resorption after bone fatigue. We carried out in vivo fatigue loading of ulna from 4- to 5-mo-old Sprague-Dawley rats treated with an apoptosis inhibitor (the pan-caspase inhibitor Q-VD-OPh) or with vehicle. Intracortical bone remodeling and osteocyte apoptosis were quantitatively assessed by standard histomorphometric techniques on day 14 after fatigue. Continuous exposure to Q-VD-OPh completely blocked both fatigue-induced apoptosis and the activation of osteoclastic resorption, whereas short-term caspase inhibition during only the first 2 days after fatigue resulted in >50% reductions in both osteocyte apoptosis and bone resorption. These results (1) show that osteocyte apoptosis is necessary to initiate intracortical bone remodeling in response to fatigue microdamage, (2) indicate a possible dose-response relationship between the two processes, and (3) suggest that early apoptotic events after fatigue-induced microdamage may play a substantial role in determining the subsequent course of tissue remodeling

Topics: Original Articles
Publisher: Amer Soc Bone & Mineral Res.
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Provided by: PubMed Central
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